The work in this proposal will attempt to document, primarily experimentally, the influence of genetic determinants in the development of the hypertension (HT) commonly described as "renal". Two unique strains of rats that possess opposite genetic propensities for HT will be used. Indirect evidence suggests that the kidneys of the HT- resistant (R) strain are more anti-hypertensive than those from the HT- Sensitive (S) strain which in turn are more HT-promoting than those from the R strain. The specific influence of the kidney will be assessed by transplanting kidneys between strains as well as by inducing renal parenchymal injury in both by (a) pyelonephritis, (b) anti-kidney serum nephritis, and (c) transient ischemia. If BP can be modified predictably, depending upon the strain from which the homograft derives, this will be direct evidence that the pro- and anti-hypertensive functions of the kidney are under genetic control. Similar evidence will derive if the development of "renal" HT associated with parenchymal injury is modified by genetic predisposition for or against HT. Finally, we wish to determine whether pads of musculo-elastic hyperplasia, observed at sites of arteriolar branching in the kidneys of S rats, play a role in the pathogenesis of malignant HT in these rats as well as man by functioning as "micro-Goldblatt clamps". Correlations between the frequency of these pads and HT will be made in rats with different genetic backgrounds (R and S, back cross, test cross) and in humans with and without HT including those with and without a strong family history of HT.